Originally published by 2 Minute Medicine^® (view original article). Reused on AccessMedicine with permission.

1. Communities with mass administration of three-dose azithromycin experienced a decrease in the prevalence of active yaws compared to communities with target treatment.

2. Yaws was shown not to be eliminated after a three-dose azithromycin treatment.

Evidence Rating Level: 1 (Excellent)

Study Rundown:

Yaws is a bacterium-caused disease afflicting children in low-income, tropical communities. Recent evidence has suggested that while oral azithromycin is effective in treating yaws, a single dose may not be sufficient for its eradication. Therefore, this study sought to investigate whether three rounds of mass administration of azithromycin would be a more effective regimen in these communities. In this cluster-randomized trial, communities with endemic areas of yaws in Papua New Guinea were randomized to either receive mass administration of three-dose azithromycin or target treatment only. The primary outcomes were the prevalence of active and latent cases of yaws. Secondary outcomes analyzed the genetic diversity of yaws, prevalence of macrolide-resistant cases, and of other infectious ulcers. The study found that the three-dose regimen of mass administration of azithromycin was superior in reducing the prevalence of both latent and active cases of yaws compared to communities receiving targeted treatment only. No differences in other infectious ulcers were found between the two groups. Given that the study found 3 cases of yaws with macrolide-resistance mutations amongst the experimental group, careful monitoring of these resistant strains is warranted. Taken together, the study supports the mass administration of three-dose azithromycin in yaws-endemic communities. The conclusions of this trial are limited by the fact that these trends can be attributed to more doses being administered in the experimental group, and no follow-up data due to the COVID-19 pandemic.

Click to read the study in NEJM

Relevant Reading: Re-emergence of yaws after single mass azithromycin treatment followed by targeted treatment: a longitudinal study

In-Depth [randomized controlled trial]:

In this open-trial, cluster-randomized, community-based trial, 38 communities in Papua New Guinea endemic for yaws were randomized in a 1:1 ratio to either receive mass administration of three rounds of oral azithromycin (at baseline, 6 months, and 12 months), or targeted therapy to active cases only, respectively. The primary objective was to assess the differences in the prevalence of both latent and active yaws in the communities at 18 months between the two groups. In total, the control group received 24,848 total doses of azithromycin, mostly in round 1, and the experimental group received a total of 59,852 doses across three rounds. The study found that the experimental group receiving mass administration saw a greater reduction in yaws prevalence compared to the control group (relative risk [RR], 4.08; 95% confidence interval [CI], 1.9 to 8.76). The experimental group also saw a lower prevalence compared to the control group as measured by positive serologic tests (RR, 2.03; 95% CI, 1.12 to 3.7). Secondary outcomes analyzed the genetic diversity of yaws, prevalence of macrolide-resistant cases, and of other infectious ulcers. In both groups, genetic diversity was decreased (p=0.22) after the 18 month study period with the J11 allelic profile. Three instances of the A2058G mutation, associated with macrolide resistance, were found in the experimental group. Finally, both groups experienced a similar prevalence of infectious ulcers not caused by T. pallidum, the primary bacterium responsible for yaws.

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